Colonic Epithelial Cell Plasma Membranes. The colon is recognized as an important organ with regard to both normal physiological and pathological processes. Elucidation of its plasma membranes structure should greatly aid in further understanding these processes. In addition, cell surface changes in colonic epithelial cells assume added importance in view of the greater incidence of malignant transformation in this organ. We therefore propose to first isolate colonic epithelial cells from the heterogeneous population of cells found in this organ by methods already devised by the Principal Investigator. Crypt and surface epithelial cells from proximal and distal rat colon will also be separated. Lumenal and basolateral plasma membranes will then be isolated and purified. Each of these membranes biochemical composition including carbohydrate, protein, lipid, glycoprotein and glycolipid will be analyzed. In addition, each membranes "fluidity" and protein and glycoprotein turnover and biosynthesis will be investigated during differentiation. After this is accomplished in the "normal" rat colon, animals will be treated with the procarcinogen 1,2 Dimethylhydrazine with appropriate controls. Epithelial cells from tumors, "transitional mucosa" and from "normal" mucosa remote from tumors will then be separated and their plasma membranes isolated. These membranes will then have their biochemical composition (see above) analyzed. Tumor membranes will also be studied with regard to their protein and glycoprotein turnover and biosynthesis. It is anticipated that there should be differences between the normal and tumor, "transitional mucosa" and "normal" mucosa remote from the tumor membrane's composition which might be useful in detecting early or "premalignant" changes. Compositional differences as well as differences in protein and glycoprotein turnover and biosynthesis between "normal" and tumor membranes might also further aid in our understanding of the process of malignant transformation.